Contrasting molecular composition and channel properties of AMPA receptorson chick auditory and brainstem motor neurons

1. Neurons in the brainstem auditory pathway exhibit a number of specializa tions for transmitting signals reliably at high rates, notably synaptic AMP A receptors with very rapid kinetics. Previous work has not revealed a comm on structural pattern shared by the AMPA receptors of auditory neurons that could account for their distinct functional properties. 2. We have used whole-cell patch-clamp recordings, mRNA analysis, immunoflu orescence, Western blots and agonist-evoked cobalt uptake to compare AMPA r eceptors on the first-, second- and third-order neurons in the chick ascend ing auditory pathway with those on brainstem motor neurons of the glossopha ryngeal/vagal nucleus, which have been shown to have very slow desensitizat ion kinetics. 3. The results indicate that the AMPA receptors of the cochlear ganglion, n ucleus magnocellularis and nucleus laminaris share a number of structural a nd functional properties that distinguish them from the AMPA receptors of b rainstem motor neurons, namely a lower relative abundance of glutamate rece ptor (GluR)2 transcript and much lower levels of GluR2 immunoreactivity, hi gher relative levels of GluR3 flop and GluR4 flop, lower relative abundance of the C-terminal splice variants GluR4c and 4d, less R/G editing of GluR2 and 3, greater permeability to calcium, predominantly inwardly rectifying I-V relationships, and greater susceptibility to block by Joro spider toxin . 4. We conclude that the AMPA receptors of auditory neurons acquire rapid ki netics from their high content of GluR3 flop and GluR4 flop subunits and th eir high permeability to Ca2+ from selective post-transcriptional suppressi on of GluR2 expression.